Prenatal exposures and cell type proportions are main drivers of FKBP5 DNA methylation in maltreated and non-maltreated children

Neurobiology of Stress, Journal Year: 2024, Volume and Issue: 33, P. 100687 - 100687

Published: Nov. 1, 2024

DNA methylation in peripheral tissues may be a relevant biomarker of risk for developing mental disorders after exposure to early life adversity. Genes involved HPA axis regulation, such as FKBP5, might play key role. In this study, we aimed identify the main drivers salivary FKBP5 cohort 162 maltreated and non-maltreated children aged 3-5 years at two measurement timepoints. We combined data from targeted bisulfite sequencing approach fine-mapping 49 CpGs regulatory regions epigenetic scores alcohol, cigarette smoke, glucocorticoids derived EPICv1 microarray. Most variability locus was explained by estimated cell type proportions well scores, most prominently glucocorticoid score. While not surviving correction multiple testing, replicated previously reported associations with CM. also detected synergistic effects both rs1360780 genotype score on hypomethylation. These were identified 3'TAD, distal region which is extensively covered Illumina arrays, emphasizing need fine mapping approaches. Additionally, associated childhood maltreatment, maternal disorders, pregnancy complications, thereby highlighting role signaling consequences results underscore assess heterogeneity assessments show impact exposures beyond just maltreatment exposure.

Language: Английский

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Neurobiological Consequences of Early Life Stress

Springer eBooks, Journal Year: 2023, Volume and Issue: unknown, P. 175 - 190

Published: Jan. 1, 2023

Language: Английский

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3 Biologische Einbettung von traumatischen Erfahrungen in der Kindheit: Relevanz von früher Intervention zur Verhinderung von Langzeitfolgen

Vandenhoeck & Ruprecht eBooks, Journal Year: 2023, Volume and Issue: unknown, P. 39 - 95

Published: Sept. 3, 2023

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Leveraging DNA Methylation to Predict Treatment Response in Major Depressive Disorder: A Critical Review

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 2, 2023

Abstract Background Major depressive disorder (MDD) is a debilitating and prevalent mental with high disease burden. Despite wide array of different treatment options, many patients do not respond to initial attempts. Selection the most appropriate remains significant clinical challenge in psychiatry, highlighting need for development biomarkers predictive utility. Recently, epigenetic modification DNA methylation (DNAm) has emerged be great interest as potential predictor MDD outcomes. Here we review efforts date that seek identify DNAm signatures associated response individuals MDD. Methods Searches were conducted databases PubMed, Scopus, Web Science concepts keywords major disorder, methylation, antidepressants, psychotherapy, cognitive behavior therapy, electroconvulsive transcranial magnetic stimulation, brain stimulation therapies. Results We identified 31 studies implicating patterns The majority ( N =25) are focused on selected target genes exploring outcomes pharmacological treatments N=22 ) few assessing therapy N=3 ). Additionally, there genome-scale N=6 characterize Limitations There relative dearth investigating relation or stimulation; importantly, existing have limited sample sizes. Conclusions Given heterogeneity both methods results date, additional before findings can inform decisions.

Language: Английский

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Within-subject changes in methylome profile identify individual signatures of early-life adversity, with a potential to predict neuropsychiatric outcome

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Dec. 19, 2023

Adverse early-life experiences (ELA), including poverty, trauma and neglect, affect a majority of the world's children. Whereas impact ELA on cognitive emotional health throughout lifespan is well-established, it not clear how distinct types influence child development, there are no tools to predict for an individual their vulnerability or resilience consequences ELAs. Epigenetic markers DNA-methylation profiles peripheral cells may encode provide predictive outcome marker. However, rapid dynamic changes in DNA methylation childhood inter-individual variance human genome pose barriers identifying predicting outcomes exposure. Here, we examined relation several dimensions methylation, using longitudinal within-subject design high threshold hope mitigating above challenges.

Language: Английский

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